We have found in the guinea pig a second insulin which is natural to the extrapancreatic tissues and is not found in plasma. This insulin has biological activity and immunoreactivity similar to typical mammalian insulins, in marked contrast to the bizarre secretory insulin found in the guinea pig pancreas. These data provide evidence for the extrapancreatic synthesis of insulin and provide new explanations for the mystery of insulin evaluation in the hystricomorph rodents. A substance extracted from drosophila and earthworms is very similar to mammal insulins.